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A synonymous variation in protease-activated receptor-2 is associated with atopy in Korean children

 Ji Hyun Lee  ;  Kyung Won Kim  ;  Myung Hyun Sohn  ;  Min Goo Lee  ;  Kyung Hwan Kim  ;  Kyu-Earn Kim  ;  Mi Na Kim  ;  So Won Kim  ;  Seung-Hyun Kim  ;  Hae-Sim Park  ;  Keun-Hwa Lee  ;  Jaechun Lee  ;  Heon Yung Gee 
 Journal of Allergy and Clinical Immunology, Vol.128(6) : 1326-3, 2011 
Journal Title
 Journal of Allergy and Clinical Immunology 
Issue Date
BACKGROUND: Atopic diseases are the most common chronic diseases of childhood, and the genetics of atopy are complex and heterogeneous. Protease-activated receptor-2 (PAR-2) is involved in various inflammatory diseases, but the association of PAR-2 with allergic diseases remains unclear. OBJECTIVE: To examine the contribution of genetic variation of PAR-2 to atopic phenotypes in the Korean childhood cohort. METHODS: We identified PAR-2 variations in a Korean population and conducted association analyses by using 316 unrelated atopic and 210 nonatopic subjects. We analyzed serum IgE and total eosinophil count levels and examined PAR-2 mRNA and protein expression levels. RESULTS: In the case-control association analysis, atopy was significantly associated with a single c.621C>T (p.I207I, rs631465) polymorphism of PAR-2 (P = .001, odds ratio = 1.95). Subjects with the c.621T risk allele had significantly higher serum IgE (P = .004) and total eosinophil count (P = .03) levels. Moreover, the positive association of c.621T was reproduced in the replication study (P = .01, joint P value of the replication < .001). An in silico analysis of RNA secondary structure prediction revealed that the C to T conversion at c.621 greatly increased predicted PAR-2 mRNA stability. This was also confirmed by an in vitro assay for mRNA stability. Furthermore, following an in vivo approach on gene expression in PBMCs showed that the expression levels of PAR-2 mRNA and protein in subjects with the c.621CT or TT genotype were significantly higher than in those with the c.621CC genotype. CONCLUSIONS: These results indicate that the synonymous c.621C>T polymorphism in PAR-2 might be associated with the risk of atopy, potentially by altering PAR-2 gene expression.
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실)
1. Journal Papers (연구논문) > 5. Research Institutes (연구소) > Research Center for Human Natural Defense System (생체방어연구센터)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Pediatrics (소아청소년과학교실)
Yonsei Authors
김경원(Kim, Kyung Won) ; 김경환(Kim, Kyung Hwan) ; 김규언(Kim, Kyu Earn) ; 김미나(Kim, Mina) ; 김소원(Kim, So Won) ; 손명현(Son, Myung Hyun) ; 이민구(Lee, Min Goo) ; 이지현(Lee, Ji Hyun) ; 지헌영(Gee, Heon Yung)
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